The epidemiological evidence that populations consuming diets rich in Omega(Omega)-3 fatty acids derived from marine animals have lower plasma lipid levels and increased bleeding times has now been confirmed in metabolic balance studies. Normal and hyperlipidemic humans were fed three different diets: "saturated" fat; high "Omega-3" fatty acids from salmon and fish oil; and a high "Omega-6' diet from safflower oil. The "high Omega-3" diet lowered plasma cholesterol, LDL, triglyceride and VLDL versus the control diet. The VLDL lowering effect was especially pronounced in hypertriglyceridemic patients (types II-b, IV and V); no triglyceride lowering occurred from the "Omega-6" diet. The "high Omega-3" diet was antithrombotic in that bleeding times increased and platelet aggregation was reduced in contrast to both control diets (the saturated fat and Omega-6 diets). The proposed new studies were designed to explore the mechanisms of the hypotriglyceridemic and platelet effects of Omega-3 fatty acids in human beings under controlled dietary conditions. The synthesis and removal of plasma triglyceride, VLDL and LDL would be determined in labelled turnover studies. The effects of Omega-3 fatty acids upon the synthesis of triglyceride and VLDL would be explored in primary liver cell cultures from experimental animals. The absorption of dietary Omega-3 fatty acids into the body and subsequent chylomicron formation and clearance would be measured in both humans and rats. The minimum amount of dietary Omega-3 fatty acids which would affect the plasma lipids and platelet function would be determined. The long term efficacy and toxicity Omega-3 fatty acids would be evaluated in hyperlipidemic patients. Their effects upon platelet count, size and composition would be measured. In addition, thromboxane and prostacyclin survival would be studied in plasma during fish oil and control periods. In particular, the reason for the thrombocytopenic effect of dietary Omega-3 fatty acids will be explored by radio-labelled platelet turnover studies. Since this unique class of dietary fatty acids may potentially be important in preventing and treating atherosclerotic and thrombotic diseases, it is now necessary to establish mechanisms of action, long term efficacy and possible untoward effects.